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      Engineering precision nanoparticles for drug delivery

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          Abstract

          In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

          Abstract

          Advances in nanoparticle design could make substantial contributions to personalized and non-personalized medicine. In this Review, Langer, Mitchell, Peppas and colleagues discuss advances in nanoparticle design that overcome heterogeneous barriers to delivery, as well as the challenges in translating these design improvements into personalized medicine approaches.

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          Most cited references293

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          Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

          Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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            Double-slit photoelectron interference in strong-field ionization of the neon dimer

            Wave-particle duality is an inherent peculiarity of the quantum world. The double-slit experiment has been frequently used for understanding different aspects of this fundamental concept. The occurrence of interference rests on the lack of which-way information and on the absence of decoherence mechanisms, which could scramble the wave fronts. Here, we report on the observation of two-center interference in the molecular-frame photoelectron momentum distribution upon ionization of the neon dimer by a strong laser field. Postselection of ions, which are measured in coincidence with electrons, allows choosing the symmetry of the residual ion, leading to observation of both, gerade and ungerade, types of interference.
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              Analysis of nanoparticle delivery to tumours

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                Author and article information

                Contributors
                mjmitch@seas.upenn.edu
                peppas@che.utexas.edu
                rlanger@mit.edu
                Journal
                Nat Rev Drug Discov
                Nat Rev Drug Discov
                Nature Reviews. Drug Discovery
                Nature Publishing Group UK (London )
                1474-1776
                1474-1784
                4 December 2020
                : 1-24
                Affiliations
                [1 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Department of Bioengineering, , University of Pennsylvania, ; Philadelphia, PA USA
                [2 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Abramson Cancer Center, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [3 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Institute for Immunology, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [4 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Cardiovascular Institute, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [5 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Institute for Regenerative Medicine, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [6 ]ISNI 0000 0004 1936 9924, GRID grid.89336.37, Department of Biomedical Engineering, , The University of Texas at Austin, ; Austin, TX USA
                [7 ]ISNI 0000 0004 1936 9924, GRID grid.89336.37, Department of Chemical Engineering, , The University of Texas at Austin, ; Austin, TX USA
                [8 ]ISNI 0000 0004 1936 9924, GRID grid.89336.37, Department of Pediatrics, , The University of Texas at Austin, ; Austin, TX USA
                [9 ]ISNI 0000 0004 1936 9924, GRID grid.89336.37, Department of Surgery and Perioperative Care, , The University of Texas at Austin, ; Austin, TX USA
                [10 ]ISNI 0000 0004 1936 9924, GRID grid.89336.37, Department of Molecular Pharmaceutics and Drug Delivery, , The University of Texas at Austin, ; Austin, TX USA
                [11 ]ISNI 0000 0001 2341 2786, GRID grid.116068.8, Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, , Massachusetts Institute of Technology, ; Cambridge, MA USA
                Author information
                http://orcid.org/0000-0002-3628-2244
                http://orcid.org/0000-0001-7322-7829
                http://orcid.org/0000-0003-4255-0492
                Article
                90
                10.1038/s41573-020-0090-8
                7717100
                33277608
                4276ba51-129c-40b0-b379-c0a1fd55c69e
                © Springer Nature Limited 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 16 October 2020
                Categories
                Review Article

                biotechnology,nanoparticles,biomedical engineering,drug delivery

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